Suppression of Nucleotidyl Cyclase 1 Enzyme (gNC1) Activity of Giardia lamblia Through the Use of Native Argentinean Plant Extracts Containing Rosmarinic Acid

AGOSTINA CIANCI ROMERO; ESTEBAN G. VEGA HISSI; ADELA MARÍA LUJÁN; AGUSTÍN YANEFF; CARLOS DAVIO; MARÍA CECILIA CARPINELLA; RICARDO DANIEL ENRIZ; ADOLFO ZURITA

San Juan

Congreso; XLI Reunión Científica Anual de la Sociedad de Biología de Cuyo.; 2023

Sociedad de Biología de Cuyo.

Giardiasis is a foodborne illness caused by the intestinal parasite Giardia lamblia (G. lamblia) and is mainly contracted through the ingestion of water and raw food contaminated with the cysts of this parasite. Currently, the lack of effective therapies against G. lamblia underscores the importance of researching and developing new chemical compounds to combat this significant pathogen. In previous studies, it has been shown that the second messenger cAMP plays a crucial role in regulating cell growth and differentiation processes in G. lamblia. Therefore, we believe that the adenylyl cyclase enzyme gNC1 would be a crucial target for future therapies. In the quest for potential inhibitors of gNC1, we explored the effects of plant extracts from the native flora of the province of Córdoba, Argentina. To this end, we conducted gNC1 enzymatic inhibition assays using extracts from the species Lepechinia meyenii, Lepechinia floribunda, Acyrocline satureioides, Baccharis coridifolia, Lithrea molleoides and Prosopis alba. Except for P. alba, all the extracts effectively blocked the enzyme´s activity when applied at 250 μg/mL, with inhibition percentages ranging between 76.5% and 96.2%. Among these, the extracts of L. floribunda and L. meyenii were the most potent, exhibiting inhibitory percentages greater than 92% and IC50 values of 9.4 and 31.3 μg/mL, respectively. Through in silico analysis of the active compounds within these extracts, we identified rosmarinic acid (RA) as the mainly compound responsible for gNC1 inhibition. This was later confirmed experimentally, as we found that RA is a potent competitive inhibitor of gNC1, with an IC50 of 10.1 μM. These results suggest that the use of natural extracts provides a valid alternative for discovering initial compounds that can be employed in future therapeutic treatments against giardiasis.